Byung Ho Kim

Mutational abrogation of the PTEN/MMAC1 gene in gastrointestinal polyps in patients with Cowden disease

BACKGROUND & AIMS To understand the molecular etiology of Cowden disease-associated gastrointestinal polyps, we analyzed the mutational status of PTEN/MMAC1, a recently identified Cowden disease gene located at 10q23, in gastric hamartomas, colonic adenoma, and juvenile polyps of 3 patients with Cowden disease. METHODS Messenger RNA expression, gene deletion, and sequence alteration of PTEN/MMAC1 were evaluated by quantitative polymerease chain reaction (PCR), PCR-single-strand conformation polymorphism, and sequencing analysis. RESULTS Germline missense mutation at codon 289 (AAA to GAA, Lys to Glu) and deletion of the wild-type allele were detected in the polyps of 2 patients with Cowden disease in the same family. Germline allelic deletion and transcriptional silencing of the remaining allele, probably caused by abnormal methylation, were also observed in a gastric hamartoma of 1 patient. CONCLUSIONS The germline mutation and alteration of the remaining allele observed in this study strongly support that PTEN/MMAC1 functions as a tumor suppressor in Cowden disease. This study is the first to show that the mutational abrogation of PTEN/MMAC1 plays a causal role in the genesis of gastrointestinal polyps in Cowden disease, providing molecular genetic evidence that colonic adenoma, juvenile polyp, and gastric hamartoma could be included in the manifestations of Cowden disease.

Decreased trabecular bone mineral density in newly diagnosed inflammatory bowel disease patients in Korea

Background : Decreased bone mineral density (BMD) is common in Western patients with inflammatory bowel disease (IBD). However, BMD has never been studied in Asia where the demographic and socio‐economic status are different from the West. The aim of this study was to investigate the prevalence and mechanisms of osteopenia in newly diagnosed Korean patients with IBD.

Delta 13C-urea breath test value is a useful indicator for Helicobacter pylori eradication in patients with functional dyspepsia

Background: Eradication of Helicobacter pylori is not routinely recommended for the symptomatic relief and the prevention of gastric cancer in patients with functional dyspepsia. The present study investigated a useful indicator of H. pylori eradication in such patients by determining the optimal cutoff value of a 13C‐urea breath test (UBT).

Autoimmune Hepatitis in a Patient with Myasthenia Gravis and Thymoma – a Report on the First Case in Korea

Myasthenia gravis is an autoimmune disease that results from an antibody-mediated reaction and occurs with thymoma in 15% of patients. It is very rarely associated with autoimmune hepatitis. Four cases of myasthenia gravis with autoimmune hepatitis have been reported in the world, We recently experienced a case of 30-year-old man with myasthenia gravis associated with thymoma and autoimmune hepatitis. This condition is the first case that has not been reported previously in Korea. We report this rare condition along with a brief review of the literature.

Sacroiliitis Is Common in Crohn's Disease Patients with Perianal or Upper Gastrointestinal Involvement

BACKGROUND/AIMS Sacroiliitis (SI) is one of the most frequent extraintestinal manifestations in inflammatory bowel disease (IBD) patients, but the exact prevalence has not been evaluated in Asia. There are few data on the association between SI and other clinical features of IBD. The prevalence of SI was evaluated using computed tomography (CT) and the phenotypic parameters associated with SI in Korean IBD patients were determined. METHODS Eighty-two patients with ulcerative colitis (UC) and 81 patients with Crohns disease (CD) were evaluated clinically. The presence of SI was evaluated using bone window setting of abdomino-pelvic CT images by two radiologists. RESULTS The prevalence rates of SI were 12.2% and 21.0% in the UC and CD groups, respectively. There was no relationship between the localization or extent of intestinal inflammation and the presence of SI in the UC group. Multivariate analyses confirmed that perianal and upper-gastrointestinal (from the mouth through to the jejunum) diseases were associated with the occurrence of SI in the CD group (p=0.026 and p=0.047, respectively). CONCLUSIONS SI was as common among Korean IBD patients as among Western patients. Perianal or upper-gastrointestinal involvement is associated with SI in CD patients.

Clinical features and outcomes of gastric variceal bleeding: retrospective Korean multicenter data

Background/Aims While gastric variceal bleeding (GVB) is not as prevalent as esophageal variceal bleeding, it is reportedly more serious, with high failure rates of the initial hemostasis (>30%), and has a worse prognosis than esophageal variceal bleeding. However, there is limited information regarding hemostasis and the prognosis for GVB. The aim of this study was to determine retrospectively the clinical outcomes of GVB in a multicenter study in Korea. Methods The data of 1,308 episodes of GVB (males:females=1062:246, age=55.0±11.0 years, mean±SD) were collected from 24 referral hospital centers in South Korea between March 2003 and December 2008. The rates of initial hemostasis failure, rebleeding, and mortality within 5 days and 6 weeks of the index bleed were evaluated. Results The initial hemostasis failed in 6.1% of the patients, and this was associated with the Child-Pugh score [odds ratio (OR)=1.619; P<0.001] and the treatment modality: endoscopic variceal ligation, endoscopic variceal obturation, and balloon-occluded retrograde transvenous obliteration vs. endoscopic sclerotherapy, transjugular intrahepatic portosystemic shunt, and balloon tamponade (OR=0.221, P<0.001). Rebleeding developed in 11.5% of the patients, and was significantly associated with Child-Pugh score (OR=1.159, P<0.001) and treatment modality (OR=0.619, P=0.026). The GVB-associated mortality was 10.3%; mortality in these cases was associated with Child-Pugh score (OR=1.795, P<0.001) and the treatment modality for the initial hemostasis (OR=0.467, P=0.001). Conclusions The clinical outcome for GVB was better for the present cohort than in previous reports. Initial hemostasis failure, rebleeding, and mortality due to GVB were universally associated with the severity of liver cirrhosis.

Percutaneous Endoscopic Gastrostomy Prevents Gastroesophageal Reflux in Patients with Nasogastric Tube Feeding: A Prospective Study with 24-Hour pH Monitoring

Background/Aims Percutaneous endoscopic gastrostomy (PEG) has been widely used for patients with swallowing dysfunction. However, its beneficial effects in the treatment of gastroesophageal reflux (GER) are controversial. The aim of this study was to evaluate the effect of PEG on the prevention of GER in patients with nasogastric tube (NGT) feeding. Methods Continuous 24-hour pH monitoring was performed prospectively in 21 patients receiving NGT feeding before and 7.3±2.2 days after PEG placement to compare the severity of GER. Results We studied 21 patients with a mean age of 59.8±14.1 years. The mean duration of NGT placement was 5.8±5.4 months. The causes of swallowing dysfunction included cerebral infarction, cerebral hemorrhage and other central nervous system (CNS) lesions. When all of the patients were considered, there were no significant differences in reflux parameters after PEG placement compared to before PEG placement. However, all seven patients who had preexisting GER showed significant improvement (p<0.05) of the reflux parameters, including the frequency of acid reflux, duration of acid reflux, total time with a pH below 4.0 and the fraction of time with a pH below 4.0, after PEG placement. Conclusions PEG might prevent GER in patients receiving NGT feeding, especially in those patients with GER.

IL-1β and IL-8, matrix metalloproteinase 3, and pepsinogen secretion before and after H. pylori eradication in gastroduodenal phenotypes

Objective. Relations between host genetic factors and clinical outcomes of Helicobacter pylori infection are variable among ethnicities. The aim of this study was to examine gastric mucosal cytokines, matrix metalloproteinase 3 (MMP-3), and serum pepsinogen levels before and after eradication of H. pylori according to IL-1B genotypes and benign gastroduodenal phenotypes in a Korean population. Material and methods. A total of 349 Koreans including H. pylori-infected subjects (n=230) and H. pylori-negative controls (n=119) were enrolled. The former subjects were classified into groups according to the presence of non-atrophic gastritis (n=74), atrophic gastritis (n=56), gastric ulcer (n=37), and duodenal ulcer (n=63). IL-1B polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Gastric mucosal IL-1β, IL-8, and MMP-3, and serum pepsinogen I and II levels were measured by ELISA and radioimmunoassay, respectively. Results. There were no significant differences between the IL-1B–31/–511 haplotype (TT/CC, CT/CT, and CC/TT) frequencies among the H. pylori-positive and −negative groups. The genotypes of IL-1B–31/–511 polymorphisms did not affect clinical phenotypes, inflammatory cytokines, MMP-3, and pepsinogen secretion. Subjects with H. pylori-infected atrophic gastritis exhibited significantly higher basal levels of cytokines and a lower pepsinogen I/II ratio than those of other groups. Following H. pylori eradication, inflammatory cytokines significantly decreased and the pepsinogen I/II ratio increased in all groups. Conclusions. Mucosal inflammatory cytokines, MMP-3, and pepsinogen secretion are related to gastroduodenal phenotypes but not to IL-1B genotypes. Eradication of H. pylori can reduce mucosal inflammation and restore pepsinogen secretion.

Spontaneous rupture of a sigmoid colon gastrointestinal stromal tumor manifesting as pneumoretroperitoneum with localized peritonitis: Report of a case

Colonic gastrointestinal stromal tumors (GISTs) account for only 5%–10% of tumors arising in the digestive tract. Spontaneous rupture is a very rare manifestation of a GIST; however, we report what to our knowledge is the first documented case of pneumoretroperitoneum caused by the rupture of a GIST. A 77-year-old woman was admitted to our hospital with acute abdominal pain and hematochezia. Colonoscopy showed luminal narrowing in the sigmoid colon, but no definite mucosal defect. Computed tomography (CT) showed an air-containing heterogeneous mass, 9.7 × 9.3 cm, in the pelvic cavity and a small amount of air in the retroperitoneum. Emergency laparotomy revealed a ruptured sigmoid colonic GIST with localized peritonitis. Pathologic examination confirmed that the tumor was composed mainly of round epithelioid cells. It was immunohistochemically positive for CD34 and negative for C-kit protein. This report describes how we successfully managed pneumoretroperitoneum with localized peritonitis caused by the spontaneous rupture of an epithelioid GIST originating from the sigmoid colon.

Epidemiological changes in hepatitis A in Korea: increasing age and its effect on clinical outcomes

Korea has recently experienced an increasing number of acute hepatitis A cases. We investigated the dynamics of hepatitis A and changes in the mean age of patients in a hospital in Seoul, Korea. Mean age increased consistently from 19 years in 1996 to 30 years in 2009 (P < 0·0001). Between two acute hepatitis A outbreaks in 1998-1999 and in 2008-2009, mean age increased from 23 to 30 years (P < 0·001). However, the hepatitis A clinical outcomes were similar between the outbreaks. Duration of hospital stay, creatinine level and prothrombin time did not differ. Throughout the study period, individuals born in the 1970s and 1980s comprised the largest proportion (84%) of patients. As this susceptible generation ages, the mean age of hepatitis A patients in Korea will increase consistently. However, at present, the impact of increasing age on clinical outcomes is not apparent.